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"text": "\n149812\nGenetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.\n\nHou, L\n\nHeilbronner, U\n\nDegenhardt, F\n\nAdli, M\n\nAkiyama, K\n\nAkula, N\n\nArdau, R\n\nArias, B\n\nBacklund, L\n\nBanzato, CE\n\nBenabarre, A\n\nBengesser, S\n\nBhattacharjee, AK\n\nBiernacka, JM\n\nBirner, A\n\nBrichant-Petitjean, C\n\nBui, ET\n\nCervantes, P\n\nChen, GB\n\nChen, HC\n\nChillotti, C\n\nCichon, S\n\nClark, SR\n\nColom, F\n\nCousins, DA\n\nCruceanu, C\n\nCzerski, PM\n\nDantas, CR\n\nDayer, A\n\nÉtain, B\n\nFalkai, P\n\nForstner, AJ\n\nFrisén, L\n\nFullerton, JM\n\nGard, S\n\nGarnham, JS\n\nGoes, FS\n\nGrof, P\n\nGruber, O\n\nHashimoto, R\n\nHauser, J\n\nHerms, S\n\nHoffmann, P\n\nHofmann, A\n\nJamain, S\n\nJiménez, E\n\nKahn, JP\n\nKassem, L\n\nKittel-Schneider, S\n\nKliwicki, S\n\nKönig, B\n\nKusumi, I\n\nLackner, N\n\nLaje, G\n\nLandén, M\n\nLavebratt, C\n\nLeboyer, M\n\nLeckband, SG\n\nJaramillo, CA\n\nMacQueen, G\n\nManchia, M\n\nMartinsson, L\n\nMattheisen, M\n\nMcCarthy, MJ\n\nMcElroy, SL\n\nMitjans, M\n\nMondimore, FM\n\nMonteleone, P\n\nNievergelt, CM\n\nNöthen, MM\n\nÖsby, U\n\nOzaki, N\n\nPerlis, RH\n\nPfennig, A\n\nReich-Erkelenz, D\n\nRouleau, GA\n\nSchofield, PR\n\nSchubert, KO\n\nSchweizer, BW\n\nSeemüller, F\n\nSeverino, G\n\nShekhtman, T\n\nShilling, PD\n\nShimoda, K\n\nSimhandl, C\n\nSlaney, CM\n\nSmoller, JW\n\nSquassina, A\n\nStamm, T\n\nStopkova, P\n\nTighe, SK\n\nTortorella, A\n\nTurecki, G\n\nVolkert, J\n\nWitt, S\n\nWright, A\n\nYoung, LT\n\nZandi, PP\n\nPotash, JB\n\nDePaulo, JR\n\nBauer, M\n\nReininghaus, EZ\n\nNovák, T\n\nAubry, JM\n\nMaj, M\n\nBaune, BT\n\nMitchell, PB\n\nVieta, E\n\nFrye, MA\n\nRybakowski, JK\n\nKuo, PH\n\nKato, T\n\nGrigoroiu-Serbanescu, M\n\nReif, A\n\nDel Zompo, M\n\nBellivier, F\n\nSchalling, M\n\nWray, NR\n\nKelsoe, JR\n\nAlda, M\n\nRietschel, M\n\nMcMahon, FJ\n\nSchulze, TG\n\nBeiträge in Fachzeitschriften\nISI:000371775000028\n26806518.0\n10.1016/S0140-6736(16)00143-4\nPMC4814312\nLithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.\n Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis.\n A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0).\n The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings.\n Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.\n Copyright © 2016 Elsevier Ltd. All rights reserved.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nReininghaus, Eva\n\n\n"
},
{
"text": "\n152092\nGenetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.\n\nOkbay, A\n\nBaselmans, BM\n\nDe Neve, JE\n\nTurley, P\n\nNivard, MG\n\nFontana, MA\n\nMeddens, SF\n\nLinnér, RK\n\nRietveld, CA\n\nDerringer, J\n\nGratten, J\n\nLee, JJ\n\nLiu, JZ\n\nde Vlaming, R\n\nAhluwalia, TS\n\nBuchwald, J\n\nCavadino, A\n\nFrazier-Wood, AC\n\nFurlotte, NA\n\nGarfield, V\n\nGeisel, MH\n\nGonzalez, JR\n\nHaitjema, S\n\nKarlsson, R\n\nvan der Laan, SW\n\nLadwig, KH\n\nLahti, J\n\nvan der Lee, SJ\n\nLind, PA\n\nLiu, T\n\nMatteson, L\n\nMihailov, E\n\nMiller, MB\n\nMinica, CC\n\nNolte, IM\n\nMook-Kanamori, D\n\nvan der Most, PJ\n\nOldmeadow, C\n\nQian, Y\n\nRaitakari, O\n\nRawal, R\n\nRealo, A\n\nRueedi, R\n\nSchmidt, B\n\nSmith, AV\n\nStergiakouli, E\n\nTanaka, T\n\nTaylor, K\n\nThorleifsson, G\n\nWedenoja, J\n\nWellmann, J\n\nWestra, HJ\n\nWillems, SM\n\nZhao, W\n\nLifeLines Cohort Study\n\nAmin, N\n\nBakshi, A\n\nBergmann, S\n\nBjornsdottir, G\n\nBoyle, PA\n\nCherney, S\n\nCox, SR\n\nDavies, G\n\nDavis, OS\n\nDing, J\n\nDirek, N\n\nEibich, P\n\nEmeny, RT\n\nFatemifar, G\n\nFaul, JD\n\nFerrucci, L\n\nForstner, AJ\n\nGieger, C\n\nGupta, R\n\nHarris, TB\n\nHarris, JM\n\nHolliday, EG\n\nHottenga, JJ\n\nDe Jager, PL\n\nKaakinen, MA\n\nKajantie, E\n\nKarhunen, V\n\nKolcic, I\n\nKumari, M\n\nLauner, LJ\n\nFranke, L\n\nLi-Gao, R\n\nLiewald, DC\n\nKoini, M\n\nLoukola, A\n\nMarques-Vidal, P\n\nMontgomery, GW\n\nMosing, MA\n\nPaternoster, L\n\nPattie, A\n\nPetrovic, KE\n\nPulkki-Råback, L\n\nQuaye, L\n\nRäikkönen, K\n\nRudan, I\n\nScott, RJ\n\nSmith, JA\n\nSutin, AR\n\nTrzaskowski, M\n\nVinkhuyzen, AE\n\nYu, L\n\nZabaneh, D\n\nAttia, JR\n\nBennett, DA\n\nBerger, K\n\nBertram, L\n\nBoomsma, DI\n\nSnieder, H\n\nChang, SC\n\nCucca, F\n\nDeary, IJ\n\nvan Duijn, CM\n\nEriksson, JG\n\nBültmann, U\n\nde Geus, EJ\n\nGroenen, PJ\n\nGudnason, V\n\nHansen, T\n\nHartman, CA\n\nHaworth, CM\n\nHayward, C\n\nHeath, AC\n\nHinds, DA\n\nHyppönen, E\n\nIacono, WG\n\nJärvelin, MR\n\nJöckel, KH\n\nKaprio, J\n\nKardia, SL\n\nKeltikangas-Järvinen, L\n\nKraft, P\n\nKubzansky, LD\n\nLehtimäki, T\n\nMagnusson, PK\n\nMartin, NG\n\nMcGue, M\n\nMetspalu, A\n\nMills, M\n\nde Mutsert, R\n\nOldehinkel, AJ\n\nPasterkamp, G\n\nPedersen, NL\n\nPlomin, R\n\nPolasek, O\n\nPower, C\n\nRich, SS\n\nRosendaal, FR\n\nden Ruijter, HM\n\nSchlessinger, D\n\nSchmidt, H\n\nSvento, R\n\nSchmidt, R\n\nAlizadeh, BZ\n\nSørensen, TI\n\nSpector, TD\n\nStarr, JM\n\nStefansson, K\n\nSteptoe, A\n\nTerracciano, A\n\nThorsteinsdottir, U\n\nThurik, AR\n\nTimpson, NJ\n\nTiemeier, H\n\nUitterlinden, AG\n\nVollenweider, P\n\nWagner, GG\n\nWeir, DR\n\nYang, J\n\nConley, DC\n\nSmith, GD\n\nHofman, A\n\nJohannesson, M\n\nLaibson, DI\n\nMedland, SE\n\nMeyer, MN\n\nPickrell, JK\n\nEsko, T\n\nKrueger, RF\n\nBeauchamp, JP\n\nKoellinger, PD\n\nBenjamin, DJ\n\nBartels, M\n\nCesarini, D\n\nBeiträge in Fachzeitschriften\nISI:000376744200009\n27089181.0\n10.1038/ng.3552\nPMC4884152\nVery few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298, 20), depressive symptoms (n = 161, 60), and neuroticism (n = 170, 11). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.\n\nKoini, Marisa\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n79148\nLarge-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.\n\nvan Meurs, JB\n\nTrikalinos, TA\n\nRalston, SH\n\nBalcells, S\n\nBrandi, ML\n\nBrixen, K\n\nKiel, DP\n\nLangdahl, BL\n\nLips, P\n\nLjunggren, O\n\nLorenc, R\n\nObermayer-Pietsch, B\n\nOhlsson, C\n\nPettersson, U\n\nReid, DM\n\nRousseau, F\n\nScollen, S\n\nVan Hul, W\n\nAgueda, L\n\nAkesson, K\n\nBenevolenskaya, LI\n\nFerrari, SL\n\nHallmans, G\n\nHofman, A\n\nHusted, LB\n\nKruk, M\n\nKaptoge, S\n\nKarasik, D\n\nKarlsson, MK\n\nLorentzon, M\n\nMasi, L\n\nMcGuigan, FE\n\nMellström, D\n\nMosekilde, L\n\nNogues, X\n\nPols, HA\n\nReeve, J\n\nRenner, W\n\nRivadeneira, F\n\nvan Schoor, NM\n\nWeber, K\n\nIoannidis, JP\n\nUitterlinden, AG\n\nGENOMOS Study\n\nBeiträge in Fachzeitschriften\nISI:000254079100019\n18349089.0\n10.1001/jama.299.11.1277\nPMC3282142\nCONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37, 34 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25, 52 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24, 12; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20, 96 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31, 35 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments. CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.\n\nObermayer-Pietsch, Barbara\n\nRenner, Wilfried\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n14216\nEscalating immunotherapy of multiple sclerosis--new aspects and practical application.\n\nRieckmann, P\n\nToyka, KV\n\nBassetti, C\n\nBeer, K\n\nBeer, S\n\nBuettner, U\n\nChofflon, M\n\nGötschi-Fuchs, M\n\nHess, K\n\nKappos, L\n\nKesselring, J\n\nGoebels, N\n\nLudin, HP\n\nMattle, H\n\nSchluep, M\n\nVaney, C\n\nBaumhackl, U\n\nBerger, T\n\nDeisenhammer, F\n\nFazekas, F\n\nFreimüller, M\n\nKollegger, H\n\nKristoferitsch, W\n\nLassmann, H\n\nMarkut, H\n\nStrasser-Fuchs, S\n\nVass, K\n\nAltenkirch, H\n\nBamborschke, S\n\nBaum, K\n\nBenecke, R\n\nBrück, W\n\nDommasch, D\n\nElias, WG\n\nGass, A\n\nGehlen, W\n\nHaas, J\n\nHaferkamp, G\n\nHanefeld, F\n\nHartung, HP\n\nHeesen, C\n\nHeidenreich, F\n\nHeitmann, R\n\nHemmer, B\n\nHense, T\n\nHohlfeld, R\n\nJanzen, RW\n\nJapp, G\n\nJung, S\n\nJügelt, E\n\nKoehler, J\n\nKölmel, W\n\nKönig, N\n\nLowitzsch, K\n\nManegold, U\n\nMelms, A\n\nMertin, J\n\nOschmann, P\n\nPetereit, HF\n\nPette, M\n\nPöhlau, D\n\nPohl, D\n\nPoser, S\n\nSailer, M\n\nSchmidt, S\n\nSchock, G\n\nSchulz, M\n\nSchwarz, S\n\nSeidel, D\n\nSommer, N\n\nStangel, M\n\nStark, E\n\nSteinbrecher, A\n\nTumani, H\n\nVoltz, R\n\nWeber, F\n\nWeinrich, W\n\nWeissert, R\n\nWiendl, H\n\nWiethölter, H\n\nWildemann, U\n\nZettl, UK\n\nZipp, F\n\nZschenderlein, R\n\nIzquierdo, G\n\nKirjazovas, A\n\nPackauskas, L\n\nMiller, D\n\nKoncan Vracko, B\n\nMillers, A\n\nOrologas, A\n\nPanellus, M\n\nSindic, CJ\n\nBratic, M\n\nSvraka, A\n\nVella, NR\n\nStelmasiak, Z\n\nSelmaj, K\n\nBartosik-Psujik, H\n\nMitosek-Szewczyk, K\n\nBelniak, E\n\nMochecka, A\n\nBayas, A\n\nChan, A\n\nFlachenecker, P\n\nGold, R\n\nKallmann, B\n\nLeussink, V\n\nMäurer, M\n\nRuprecht, K\n\nStoll, G\n\nWeilbach, FX\n\nMultiple Sclerosis Therapy Consensus Group\n\nBeiträge in Fachzeitschriften\nISI:000225610400005\n15592728.0\n10.1007/s00415-004-0537-6\nNone\nRecent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.\n\nFazekas, Franz\n\nFuchs, Siegrid\n\n\n"
},
{
"text": "\n2099\nPrognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy.\n\nKapp, KS\n\nStuecklschweiger, GF\n\nKapp, DS\n\nPoschauko, J\n\nPickel, H\n\nLahousen, M\n\nHackl, A\n\nBeiträge in Fachzeitschriften\nISI:000076681100009\n9806511.0\n10.1016/s0360-3016(98)00255-7\nNone\nPrognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP.\n Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM).\n At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, > or = 3 < 6, > or = 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels < or = 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes > or = 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p = 0.0210) and DM (p = 0.0011).\n This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.\n\n\n"
},
{
"text": "\n184763\nA Culturally Adapted SMS Text Messaging Intervention to Promote Antiretroviral Therapy Adherence Among African Americans: Protocol for a Single-Arm Trial.\n\nKohli, M\n\nPasipanodya, EC\n\nMontoya, JL\n\nMarquine, M\n\nHoenigl, M\n\nSerrano, V\n\nCushman, C\n\nGarcia, R\n\nKua, J\n\nGant, V\n\nRojas, S\n\nMoore, DJ\n\nBeiträge in Fachzeitschriften\nNone\n33300885.0\n10.2196/21592\nPMC7759437\nAfrican Americans are disproportionally affected by HIV and have poorer rates of antiretroviral therapy (ART) adherence compared to other racial or ethnic groups in the United States. Factors associated with poor HIV disease outcomes are commonly associated with sociostructural barriers that prevent engagement with and retention in HIV care. SMS text messaging interventions to promote ART adherence among predominantly non-Hispanic White persons with HIV (PWH) have been shown to be efficacious; however, limited research has been devoted to culturally tailoring interventions for underrepresented racial/ethnic groups. Considering African Americans show poorer engagement along the HIV care continuum, we developed an individualized and culturally tailored two-way SMS text messaging intervention to improve ART adherence and associated virologic suppression among African American PWH.\n In this paper we describe the protocol of a culturally tailored individualized Texting for Adherence Building (iTAB) intervention in a 24- to 48-week, single-arm study.\n We developed a culturally tailored iTAB intervention, which we are implementing in a 24- to 48-week, single-arm study. Participants were recruited from the Family Health Centers of San Diego (FHCSD), a federally qualified health center. Patient inclusion criteria were (1) receiving care at the FHCSD, (2) living with HIV, (3) self-identification as Black, African American, or of African ancestry, (4) English speaking, (5) age 18 or older, (6) currently on ART, and (7) able to provide informed consent. Study enrollment began in November 2017 and closed in July 2019. A total of 90 participants from the FHCSD enrolled in the iTAB intervention, and we anticipate completing data collection in July 2020. Participants were assisted in individualizing and customizing their SMS text message preferences at the baseline study visit. Self-assessment measures are collected at baseline, interim, and final study visits. Problems related to sending/receiving SMS text messages and barriers to ART adherence are assessed at each interim study visit. The FHCSD staff monitors and tracks participants' daily SMS text message responses to ART adherence reminders using a clinical dashboard.\n We hypothesize that the proportion of individuals achieving HIV virologic suppression (viral load <40 copies/mL) will be greater at the end of the intervention period compared to the proportion prior to study implementation. Additionally, we anticipate that rates of virologic suppression at the end of the intervention among participants receiving iTAB will be comparable to those among the general FHCSD non-African American population who did not receive iTAB. Finally, we anticipate a high response rate to iTAB SMS text messages as well as positive participant feedback at the end of the intervention with regard to the acceptability of, satisfaction with, and perceived efficacy of iTAB.\n The iTAB intervention is a novel individualized two-way SMS text messaging intervention that has been culturally tailored for use among African Americans with HIV. We anticipate that iTAB will demonstrate efficacy in future randomized control trials and will be supportive of medication adherence among other populations facing health disparities.\n DERR1-10.2196/21592.\n ©Maulika Kohli, Elizabeth C Pasipanodya, Jessica L Montoya, Maria Marquine, Martin Hoenigl, Vanessa Serrano, Clint Cushman, Rogelio Garcia, John Kua, Verna Gant, Sarah Rojas, David J Moore. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.12.2020.\n\nHönigl, Martin\n\n\n"
},
{
"text": "\n133035\nGenetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.\n\nMoayyeri, A\n\nHsu, YH\n\nKarasik, D\n\nEstrada, K\n\nXiao, SM\n\nNielson, C\n\nSrikanth, P\n\nGiroux, S\n\nWilson, SG\n\nZheng, HF\n\nSmith, AV\n\nPye, SR\n\nLeo, PJ\n\nTeumer, A\n\nHwang, JY\n\nOhlsson, C\n\nMcGuigan, F\n\nMinster, RL\n\nHayward, C\n\nOlmos, JM\n\nLyytikäinen, LP\n\nLewis, JR\n\nSwart, KM\n\nMasi, L\n\nOldmeadow, C\n\nHolliday, EG\n\nCheng, S\n\nvan Schoor, NM\n\nHarvey, NC\n\nKruk, M\n\ndel Greco M, F\n\nIgl, W\n\nTrummer, O\n\nGrigoriou, E\n\nLuben, R\n\nLiu, CT\n\nZhou, Y\n\nOei, L\n\nMedina-Gomez, C\n\nZmuda, J\n\nTranah, G\n\nBrown, SJ\n\nWilliams, FM\n\nSoranzo, N\n\nJakobsdottir, J\n\nSiggeirsdottir, K\n\nHolliday, KL\n\nHannemann, A\n\nGo, MJ\n\nGarcia, M\n\nPolasek, O\n\nLaaksonen, M\n\nZhu, K\n\nEnneman, AW\n\nMcEvoy, M\n\nPeel, R\n\nSham, PC\n\nJaworski, M\n\nJohansson, Å\n\nHicks, AA\n\nPludowski, P\n\nScott, R\n\nDhonukshe-Rutten, RA\n\nvan der Velde, N\n\nKähönen, M\n\nViikari, JS\n\nSievänen, H\n\nRaitakari, OT\n\nGonzález-Macías, J\n\nHernández, JL\n\nMellström, D\n\nLjunggren, O\n\nCho, YS\n\nVölker, U\n\nNauck, M\n\nHomuth, G\n\nVölzke, H\n\nHaring, R\n\nBrown, MA\n\nMcCloskey, E\n\nNicholson, GC\n\nEastell, R\n\nEisman, JA\n\nJones, G\n\nReid, IR\n\nDennison, EM\n\nWark, J\n\nBoonen, S\n\nVanderschueren, D\n\nWu, FC\n\nAspelund, T\n\nRichards, JB\n\nBauer, D\n\nHofman, A\n\nKhaw, KT\n\nDedoussis, G\n\nObermayer-Pietsch, B\n\nGyllensten, U\n\nPramstaller, PP\n\nLorenc, RS\n\nCooper, C\n\nKung, AW\n\nLips, P\n\nAlen, M\n\nAttia, J\n\nBrandi, ML\n\nde Groot, LC\n\nLehtimäki, T\n\nRiancho, JA\n\nCampbell, H\n\nLiu, Y\n\nHarris, TB\n\nAkesson, K\n\nKarlsson, M\n\nLee, JY\n\nWallaschofski, H\n\nDuncan, EL\n\nO'Neill, TW\n\nGudnason, V\n\nSpector, TD\n\nRousseau, F\n\nOrwoll, E\n\nCummings, SR\n\nWareham, NJ\n\nRivadeneira, F\n\nUitterlinden, AG\n\nPrince, RL\n\nKiel, DP\n\nReeve, J\n\nKaptoge, SK\n\nBeiträge in Fachzeitschriften\nISI:000336483200021\n24430505.0\n10.1093/hmg/ddt675\nPMC4038791\nQuantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.\n\nObermayer-Pietsch, Barbara\n\nTrummer, Olivia\n\n\n"
},
{
"text": "\n175798\nTHE REFERENCE SITE COLLABORATIVE NETWORK OF THE EUROPEAN INNOVATION PARTNERSHIP ON ACTIVE AND HEALTHY AGEING\n\nBousquet, J\n\nIllario, M\n\nFarrell, J\n\nBatey, N\n\nCarriazo, AM\n\nMalva, J\n\nHajjam, J\n\nColgan, E\n\nGuldemond, N\n\nPerala-Heape, M\n\nOnorato, GL\n\nBedbrook, A\n\nLeonardini, L\n\nStroetman, V\n\nBirov, S\n\nAbreu, C\n\nAbrunhosa, A\n\nAgrimi, A\n\nAlalaakkola, T\n\nAllegretti, N\n\nAlonso-Trujillo, F\n\nAlvarez-Benito, M\n\nAngioli, S\n\nApostolo, J\n\nArmitage, G\n\nArnavielhe, S\n\nBaena-Parejo, MI\n\nBamidis, PD\n\nBalenovic, A\n\nBarbolini, M\n\nBaroni, I\n\nBlain, H\n\nBernard, PL\n\nBersani, M\n\nBerti, E\n\nBogatyrchuk, L\n\nBourret, R\n\nBrehm, J\n\nBrussino, L\n\nBuhr, D\n\nBultje, D\n\nCabeza, E\n\nCano, A\n\nDe Capitani, C\n\nCarantona, E\n\nCardoso, A\n\nClavero, JIC\n\nCombe, B\n\nConforti, D\n\nCoppola, L\n\nCorti, F\n\nCoscioni, E\n\nCosta, E\n\nCrooks, G\n\nCunha, A\n\nDaien, C\n\nDantas\n\nSierra, JD\n\nDavoli, M\n\nBaraldes, AD\n\nDe Luca, V\n\nDe Nardi, L\n\nDi Ciano, M\n\nDozet, A\n\nEkinci, B\n\nErve, S\n\nEspinoza, AJM\n\nFait, A\n\nFensli, R\n\nNocelo, SF\n\nGalvez-Daza, P\n\nGaamez-Paya, J\n\nSaez, MG\n\nSanchez, IG\n\nGemicioglu, B\n\nGoetzke, W\n\nGoossens, E\n\nGeurdens, M\n\nGutter, Z\n\nHansen, H\n\nHartman, S\n\nHegendorfer, G\n\nHeikka, H\n\nHenderson, D\n\nHeran, D\n\nHirvonen, S\n\nIaccarino, G\n\nJansson, N\n\nKallasvaara, H\n\nKalyoncu, F\n\nKirchmayer, U\n\nKokko, JA\n\nKorpelainen, J\n\nKostka, T\n\nKuna, P\n\nOrtega, TL\n\nLama, CM\n\nLaune, D\n\nLauri, D\n\nLedroit, V\n\nLevato, G\n\nLewis, L\n\nLiotta, G\n\nLundgren, L\n\nLupianez-Villanueva, F\n\nMc Garry, P\n\nMaggio, M\n\nde Keenoy, EM\n\nMartinez, C\n\nMartinez-Domene, M\n\nAranaga, BML\n\nMassimilliano, M\n\nMaurizio, A\n\nMayora, O\n\nMelle, C\n\nMendez-Zorilla, A\n\nMengon, H\n\nMercier, G\n\nMercier, J\n\nMeyer, I\n\nPi-Figueras, AM\n\nMitsias, P\n\nMolloy, DW\n\nMonti, R\n\nMoro, ML\n\nMuranko, H\n\nNalin, M\n\nNobili, A\n\nNogues, M\n\nO'Caoimh, R\n\nPais, S\n\nPapini, D\n\nParkkila, P\n\nPattichis, C\n\nPavlickova, A\n\nPeiponen, A\n\nPereira, S\n\nPepin, JL\n\nJimenez, P\n\nPortheine, P\n\nPotel, L\n\nPozzi, AC\n\nQuinonez, P\n\nLauritsen, XR\n\nRamos, MJ\n\nRannali-Kontturi, A\n\nRisino, A\n\nRobalo-Cordeiro, C\n\nRolla, G\n\nRoller, R\n\nRomano, M\n\nRomano, V\n\nRuiz-Fernandez, J\n\nSaccavini, C\n\nSachinopoulou, A\n\nRubio, MJS\n\nSantos, L\n\nScalvini, S\n\nScopetani, E\n\nSmedberg, D\n\nSolana-Lara, R\n\nSoltysik, B\n\nSorlini, M\n\nStericker, S\n\nBadiale, MS\n\nTaillieu, I\n\nTervahauta, M\n\nTeixeira, A\n\nTikanmaki, H\n\nTodo-Bom, A\n\nTooley, A\n\nTuulonen, A\n\nTziraki, C\n\nUssai, S\n\nVan der Veen, S\n\nVenchiarutti, A\n\nVerdoy-Berastegi, D\n\nVerissimo, M\n\nVisconti, L\n\nVollenbroek-Hutten, M\n\nWeinzerl, K\n\nWozniak, L\n\nYorgancioglu, A\n\nZavagli, V\n\nZurkuhlen, AJ\n\nBeiträge in Fachzeitschriften\nISI:000470089500011\nNone\nNone\nNone\nSeventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs.\n\nRoller-Wirnsberger, Regina\n\n\n"
},
{
"text": "\n182868\nThe PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology.\n\nTrebicka, J\n\nFernandez, J\n\nPapp, M\n\nCaraceni, P\n\nLaleman, W\n\nGambino, C\n\nGiovo, I\n\nUschner, FE\n\nJimenez, C\n\nMookerjee, R\n\nGustot, T\n\nAlbillos, A\n\nBañares, R\n\nJanicko, M\n\nSteib, C\n\nReiberger, T\n\nAcevedo, J\n\nGatti, P\n\nBernal, W\n\nZeuzem, S\n\nZipprich, A\n\nPiano, S\n\nBerg, T\n\nBruns, T\n\nBendtsen, F\n\nCoenraad, M\n\nMerli, M\n\nStauber, R\n\nZoller, H\n\nRamos, JP\n\nSolè, C\n\nSoriano, G\n\nde Gottardi, A\n\nGronbaek, H\n\nSaliba, F\n\nTrautwein, C\n\nÖzdogan, OC\n\nFrancque, S\n\nRyder, S\n\nNahon, P\n\nRomero-Gomez, M\n\nVan Vlierberghe, H\n\nFrancoz, C\n\nManns, M\n\nGarcia, E\n\nTufoni, M\n\nAmoros, A\n\nPavesi, M\n\nSanchez, C\n\nCurto, A\n\nPitarch, C\n\nPutignano, A\n\nMoreno, E\n\nShawcross, D\n\nAguilar, F\n\nClària, J\n\nPonzo, P\n\nJansen, C\n\nVitalis, Z\n\nZaccherini, G\n\nBalogh, B\n\nVargas, V\n\nMontagnese, S\n\nAlessandria, C\n\nBernardi, M\n\nGinès, P\n\nJalan, R\n\nMoreau, R\n\nAngeli, P\n\nArroyo, V\n\nPREDICT STUDY group of the EASL-CLIF Consortium\n\nBeiträge in Fachzeitschriften\nISI:000572079900019\n32673741.0\n10.1016/j.jhep.2020.06.013\nNone\nAcute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF.\n A total of 1, 71 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded.\n Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC).\n Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS.\n NCT03056612.\n Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.\n Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n82772\nAdjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy.\n\nGnant, M\n\nMlineritsch, B\n\nLuschin-Ebengreuth, G\n\nKainberger, F\n\nKässmann, H\n\nPiswanger-Sölkner, JC\n\nSeifert, M\n\nPloner, F\n\nMenzel, C\n\nDubsky, P\n\nFitzal, F\n\nBjelic-Radisic, V\n\nSteger, G\n\nGreil, R\n\nMarth, C\n\nKubista, E\n\nSamonigg, H\n\nWohlmuth, P\n\nMittlböck, M\n\nJakesz, R\n\nAustrian Breast and Colorectal Cancer Study Group (ABCSG)\n\nBeiträge in Fachzeitschriften\nISI:000259060100017\n18718815.0\n10.1016/S1470-2045(08)70204-3\nNone\nBackground The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting. Methods ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646. Findings 404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean difference -0.119 g/cm(2) [95% Cl -0.146 to -0.0911, p<0.0001) and trochanter (-7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p<0.0001). In patients who did not receive zoledronic acid, anastrozole caused greater BM D loss than tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141 g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to -0.057], p<0.0001 for both). 2 years after the completion of treatment (median follow-up 60 months [range 15.5-96-6]), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine -6.3%, mean difference -0.067 g/cm(2) [-0.106 to -0.027], p=0.001; trochanter -4.1%, mean difference -0.03 g/cm(2) [-0.062 to 0.0011, p=0.058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0.4%, mean difference 0.004 g/cm(2) [-0.024 to 0.032]; trochanter +0.8%, mean difference 0 - 006 g/cm(2) [-0.018 to 0 - 0281) and increased BMD at 60 months at both sites (lumbar spine +4.0%, mean difference 0.039 g/cm(2) [0.005-0.075], p=0.02; trochanter +3.9%, mean difference 0.028 g/cm(2) [0.003-0.058], p=0.07) compared with baseline. Interpretation Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years.\n\nBauernhofer, Thomas\n\nBjelic-Radisic, Vesna\n\nHofmann, Guenter\n\nLuschin-Ebengreuth, Gero\n\nSamonigg, Hellmut\n\n\n"
},
{
"text": "\n113551\nA comparative performance analysis of total prostate-specific antigen, percentage free prostate-specific antigen, prostate-specific antigen velocity and urinary prostate cancer gene 3 in the first, second and third repeat prostate biopsy.\n\nAuprich, M\n\nAugustin, H\n\nBudäus, L\n\nKluth, L\n\nMannweiler, S\n\nShariat, SF\n\nFisch, M\n\nGraefen, M\n\nPummer, K\n\nChun, FK\n\nBeiträge in Fachzeitschriften\nISI:000303598400014\n21939492.0\n10.1111/j.1464-410X.2011.10584.x\nNone\nStudy Type Diagnosis (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Risk factor assessment in the repeat biopsy setting is affected by a decreasing diagnostic accuracy of each single risk factor (e.g. DRE, tPSA, %fPSA, complexed PSA, PSA density or PSAV] with increasing number of prostate biopsy sessions. PCA3 shows impressive diagnostic performance in the initial and early repeat biopsy settings. In a head-to-head comparison we demonstrate the concept that the number of previous repeat biopsy session strongly influences performance characteristics of biopsy risk factors, including PCA3. While the novel diagnostic marker would have avoided a considerable number of unnecessary biopsies in the first repeat biopsy scenario, its effects dissipated at second and = third repeat biopsies. OBJECTIVE To compare the performance characteristics of prostate cancer risk factors such as total prostate-specific antigen (tPSA), percentage free PSA (%fPSA), PSA velocity (PSAV) and urinary prostate cancer gene 3 (PCA3) at first, second and = third repeat biopsy session. PATIENTS AND METHODS Patients (n= 127) aged =70 years, with suspicious digital rectal examination (DRE) and/or persistently elevated age-specific total PSA levels (2.56.5 ng/mL) and/or suspicious prior histology (atypical small acinar proliferations [ASAPs]= two cores affected by high-grade prostatic intra-epithelial neoplasia [HGPIN]) undergoing either a first, second, or = third repeat biopsy were investigated using a 12- or 24-core biopsy scheme. PSAV (= three values collected over =12 months) was calculated using the log-slope method. PCA3 scores were assessed using the Progensa assay (R). After stratification according to the number of previous biopsies (first, second and = third), calculation of specificity, positive and negative predictive values (PPV, NPV) and the proportion of avoided unnecessary repeat biopsies (PAB) compared with tPSA at fixed sensitivity thresholds (75, 85 and 95%) were performed. Finally, accuracy estimates (area under the curve [AUC]) were quantified for each repeat biopsy scenario. RESULTS At repeat biopsy, overall prostate cancer (PCa) detection was 34.6%. At first repeat biopsy, PCA3 predicted PCa best (AUC = 0.80) and would have avoided 72.2% of repeat biopsies (75% sensitivity) compared with tPSA. At second repeat biopsy, %fPSA demonstrated the highest accuracy (AUC = 0.82) and would have avoided 66.7% of repeat biopsies (75% sensitivity) compared with tPSA. At = third repeat biopsy, again %fPSA demonstrated the highest accuracy (AUC = 0.70) and would have avoided 45.0% of repeat biopsies (75% sensitivity) compared with tPSA. The main limitation of our study resides in its small sample size. CONCLUSIONS The findings of the present study promote the concept that the number of previous repeat biopsy sessions strongly influences the performance characteristics of biopsy risk factors. Total PSA was no significant risk factor in the entire analysis. By contrast, %fPSA performed best at second and = third repeat biopsy. PSAV's diagnostic potential was reserved to patients at second and = third repeat biopsy. Finally, PCA3 demonstrated the highest diagnostic accuracy and potential to reduce unnecessary biopsies at first repeat biopsy. However, this advantage dissipated at second and = third repeat biopsy.\n\nAugustin, Herbert\n\nMannweiler, Sebastian\n\nPummer, Karl\n\n\n"
},
{
"text": "\n168007\nAnalysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder.\n\nReinbold, CS\n\nForstner, AJ\n\nHecker, J\n\nFullerton, JM\n\nHoffmann, P\n\nHou, L\n\nHeilbronner, U\n\nDegenhardt, F\n\nAdli, M\n\nAkiyama, K\n\nAkula, N\n\nArdau, R\n\nArias, B\n\nBacklund, L\n\nBenabarre, A\n\nBengesser, S\n\nBhattacharjee, AK\n\nBiernacka, JM\n\nBirner, A\n\nMarie-Claire, C\n\nCervantes, P\n\nChen, GB\n\nChen, HC\n\nChillotti, C\n\nClark, SR\n\nColom, F\n\nCousins, DA\n\nCruceanu, C\n\nCzerski, PM\n\nDayer, A\n\nÉtain, B\n\nFalkai, P\n\nFrisén, L\n\nGard, S\n\nGarnham, JS\n\nGoes, FS\n\nGrof, P\n\nGruber, O\n\nHashimoto, R\n\nHauser, J\n\nHerms, S\n\nJamain, S\n\nJiménez, E\n\nKahn, JP\n\nKassem, L\n\nKittel-Schneider, S\n\nKliwicki, S\n\nKönig, B\n\nKusumi, I\n\nLackner, N\n\nLaje, G\n\nLandén, M\n\nLavebratt, C\n\nLeboyer, M\n\nLeckband, SG\n\nLópez Jaramillo, CA\n\nMacQueen, G\n\nManchia, M\n\nMartinsson, L\n\nMattheisen, M\n\nMcCarthy, MJ\n\nMcElroy, SL\n\nMitjans, M\n\nMondimore, FM\n\nMonteleone, P\n\nNievergelt, CM\n\nÖsby, U\n\nOzaki, N\n\nPerlis, RH\n\nPfennig, A\n\nReich-Erkelenz, D\n\nRouleau, GA\n\nSchofield, PR\n\nSchubert, KO\n\nSchweizer, BW\n\nSeemüller, F\n\nSeverino, G\n\nShekhtman, T\n\nShilling, PD\n\nShimoda, K\n\nSimhandl, C\n\nSlaney, CM\n\nSmoller, JW\n\nSquassina, A\n\nStamm, TJ\n\nStopkova, P\n\nTighe, SK\n\nTortorella, A\n\nTurecki, G\n\nVolkert, J\n\nWitt, SH\n\nWright, AJ\n\nYoung, LT\n\nZandi, PP\n\nPotash, JB\n\nDePaulo, JR\n\nBauer, M\n\nReininghaus, E\n\nNovák, T\n\nAubry, JM\n\nMaj, M\n\nBaune, BT\n\nMitchell, PB\n\nVieta, E\n\nFrye, MA\n\nRybakowski, JK\n\nKuo, PH\n\nKato, T\n\nGrigoroiu-Serbanescu, M\n\nReif, A\n\nDel Zompo, M\n\nBellivier, F\n\nSchalling, M\n\nWray, NR\n\nKelsoe, JR\n\nAlda, M\n\nMcMahon, FJ\n\nSchulze, TG\n\nRietschel, M\n\nNöthen, MM\n\nCichon, S\n\nBeiträge in Fachzeitschriften\nISI:000433565000001\n29904359.0\n10.3389/fpsyt.2018.00207\nPMC5991073\nBipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2, 63 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nReininghaus, Eva\n\n\n"
},
{
"text": "\n184163\nIntravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.\n\nThomalla, G\n\nBoutitie, F\n\nMa, H\n\nKoga, M\n\nRingleb, P\n\nSchwamm, LH\n\nWu, O\n\nBendszus, M\n\nBladin, CF\n\nCampbell, BCV\n\nCheng, B\n\nChurilov, L\n\nEbinger, M\n\nEndres, M\n\nFiebach, JB\n\nFukuda-Doi, M\n\nInoue, M\n\nKleinig, TJ\n\nLatour, LL\n\nLemmens, R\n\nLevi, CR\n\nLeys, D\n\nMiwa, K\n\nMolina, CA\n\nMuir, KW\n\nNighoghossian, N\n\nParsons, MW\n\nPedraza, S\n\nSchellinger, PD\n\nSchwab, S\n\nSimonsen, CZ\n\nSong, SS\n\nThijs, V\n\nToni, D\n\nHsu, CY\n\nWahlgren, N\n\nYamamoto, H\n\nYassi, N\n\nYoshimura, S\n\nWarach, S\n\nHacke, W\n\nToyoda, K\n\nDonnan, GA\n\nDavis, SM\n\nGerloff, C\n\nEvaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators\n\nBeiträge in Fachzeitschriften\nISI:000588778800029\n33176180.0\n10.1016/S0140-6736(20)32163-2\nPMC7734592\nPatients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.\n We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.\n Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).\n In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.\n None.\n Copyright © 2020 Elsevier Ltd. All rights reserved.\n\nFandler-Höfler, Simon\n\nFazekas, Franz\n\nGattringer, Thomas\n\nPichler, Alexander\n\n\n"
},
{
"text": "\n111346\nAdjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial.\n\nGnant, M\n\nMlineritsch, B\n\nStoeger, H\n\nLuschin-Ebengreuth, G\n\nHeck, D\n\nMenzel, C\n\nJakesz, R\n\nSeifert, M\n\nHubalek, M\n\nPristauz, G\n\nBauernhofer, T\n\nEidtmann, H\n\nEiermann, W\n\nSteger, G\n\nKwasny, W\n\nDubsky, P\n\nHochreiner, G\n\nForsthuber, EP\n\nFesl, C\n\nGreil, R\n\nAustrian Breast and Colorectal Cancer Study Group, Vienna, Austria\n\nBeiträge in Fachzeitschriften\nISI:000292640200015\n21641868.0\n10.1016/S1470-2045(11)70122-X\nNone\nAnalysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid.\n ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I-II) breast cancer receiving goserelin (3.6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing.\n At a median follow-up of 62 months (range 0-114.4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid reduced risk of disease-free survival events overall (HR 0.68, 95% CI 0.51-0.91; p=0.009), although the difference was not significant in the tamoxifen (HR 0.67, 95% CI 0.44-1.03; p=0.067) and anastrozole arms (HR 0.68, 95% CI 0.45-1.02; p=0.061) assessed separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without; HR 0.67, 95% CI 0.41-1.07; p=0.09). There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone (HR 1.08, 95% CI 0.81-1.44; p=0.591), but overall survival was worse with anastrozole than with tamoxifen (46 vs 27 deaths; HR 1.75, 95% CI 1.08-2.83; p=0.02). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was reported in 601 patients (33%; 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%; 192 vs 169), headache in 280 (16%; 147 vs 133), and arthralgia in 266 (15%; 145 vs 121).\n Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen. There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer.\n AstraZeneca; Novartis.\n Copyright © 2011 Elsevier Ltd. All rights reserved.\n\nBauernhofer, Thomas\n\nLuschin-Ebengreuth, Gero\n\nPristauz-Telsnigg, Gunda\n\nStoeger, Herbert\n\n\n"
},
{
"text": "\n990\nEthics in intensive medicine\n\nList, WF\n\nBeiträge in Fachzeitschriften\nISI:A1997WZ03900002\n9229978.0\n10.1007/s001010050399\nNone\nIn more than 30 years of development of intensive care medicine (ICM), our specialty has acquired moral and ethical standpoints, although not without public pressure and discussions. Special commissions dealing, e.g., with brain death, terminal care, ethics of foregoing life-sustaining treatment in the critically ill, withholding or withdrawing mechanical ventilation, and other issues have been formed in a number of medical societies. International consensus conferences have helped to clarify some of the issues. With increasing experience, a multitude of ethical problems have arisen in ICM that have to be dealt with, such as the issue of quality of life. What is an unworthy life? Are we allowed to make judgments for our patients? What is cost-effectiveness in ICM? Other restrictions include bed and equipment shortages in the intensive care unit (ICU), the necessity for triage--undisputed in catastrophe medicine--and how one should proceed in managing elective patients? In situations of limited ICU bed availability, sicker patients will be admitted, sparing out patients who are less ill for observation and those with poor quality of life and poor prognosis. For the future, it will likely be necessary to define the patients who should be admitted to an ICU more than those who should not be admitted. An ICU treatment entitlement index would be directly proportional to the probability of successful outcome and the quality of the remaining life, and would be inversely related to costs for achieving success. The ICU outcome with survival, hospital mortality, and follow-up of ICU patients is considered. DNR (do not resuscitate), the dying patient, terminal care, terminal weaning--DNT (do not treat)--active and passive euthanasia, living wills, quality of life, and cost-effectiveness for ICU patients are defined. Their application in the ICU will be discussed and problems pointed out. Outcome predictions using scores (APACHE III, SAPS II, MPM) have been developed based on previous experience, but should only be applied to patient groups and for quality assurance in ICUs. The most frequent and difficult problem in the ICUs is the vegetative state, which requires an exact diagnosis. The differential diagnosis from other comatose states such as coma, brain death, and locked-in-syndrome is depicted. The ethics of interrupting life-sustaining treatment in critically ill patients have been worked out by a Task Force on Ethics of the Society of Critical Care Medicine (1990). A consensus was found that the patient may judge to forego therapy; ethically it is then appropriate to withhold or withdraw therapy. According to the consensus, withdrawing an already initiated treatment should not necessarily be regarded as more problematic than a decision not to initiate treatment. In my mind, however, there is a great difference between withdrawing or withholding, e.g., ventilation. A dissentive opinion by some members of the Task Force stated that hydration and nutrition other than high-technology or parenteral nutrition are key components of patient care, and should not be equated with medical intervention. The ethical problems associated with active euthanasia (physician-assisted suicide or death) as practised in the Netherlands are also discussed. In most countries this practice seems unacceptable. From 30 years experience in ICM, there are many more ethical questions and case reports without clear solutions. Care decisions for single patients in unacceptable situations should be made after medical evaluation by the intensivist with the medical team and, if possible, by the patient and/or his or her surrogate. Legislation and solutions cannot be expected for single patients, but ethics committees could be helpful in decision-making.\n\n\n"
},
{
"text": "\n1286\nValue of prognostic factors in the Austrian A-NB87 Neuroblastoma Study\n\nLadenstein, R\n\nAmbros, PF\n\nUrban, C\n\nAmbros, IM\n\nFink, FM\n\nZoubek, A\n\nGrienberger, H\n\nSchmitt, K\n\nKerbl, R\n\nHorcher, E\n\nAmann, G\n\nHöfler, G\n\nHeinzl, H\n\nGadner, H\n\nMutz, I\n\nBeiträge in Fachzeitschriften\nISI:A1996VB28100014\n8926686.0\n10.1055/s-2008-1046476\nNone\nAIMS: A multivariate analysis was performed to evaluate the impact of various prospectively evaluated risk factors. PATIENTS AND METHODS: From January 1987 to December 1993, 120 patients were registered in the study. 108/120 patients were eligible. There were 49 girls and 59 boys with a median age at diagnosis of 14 months (range, 0 to 224 months). Patients were classified according to the Evans classification system. LDH, NSE, Ferritin, N-myc amplification, 1p-deletion and ploidy were evaluated at diagnosis. Treatment intensity was based on the results of primary surgery: surgery only for 22 (20%) stage I and IIA patients (macroscopic residue without lymph node involvement), the 9 IIB patients (8, %) (macroscopic residue with lymph node involvement) had mild chemotherapy in addition (6 x VCR/CYC) and elective radiation (Rx). Stage III patients were divided into 2 groups: IIIA patients (n = 17/16%) had to have ferritin levels under 300 micrograms/ml, NSE lower than 100 ng/ml and age below 2 years at diagnosis and received 6 alternating cycles of DAMO/ MVDOC. If one of these three criteria was not fulfilled, patients were assigned to the more intensive treatment arm stage IIIB (n = 12/11%), i.e. 9 alternating cycles of DAMO/MVDOC/IPE. Stage IV pts (n = 35/32.5%) received 8 MVDOC/IPE cycles and 20 patients received megatherapy followed by stem cell reinfusion in addition. 13 stage IVs patients (12%) were registered and had elective VCR/CYC and/or liver radiation in case of poor clinical condition. The median observation time is 4.2 years (range, 1 to 7.5). RESULTS: The survival rate at 3 years was excellent for localized disease and stage IVs with survival rates of 100% for stage I/IIA and 92% for stage IVs. Stage IIIA patients had an EFS rate of 81% whereas stage IIB patients achieved only 69%. Stage IV patients reached 51%, however outcome was especially poor for stage IIIB patients (20%) due to treatment related toxicities. The toxic death rate in the study was 13% (2 surgical deaths, 8 infections, 4 multiple organ failures). Univariate analysis demonstrated the following significant unfavorable risk factors: age over 1 year at diagnosis (58/108 pts, p = 0.006), NSE > 100 ng/ml (26/95 pts, p < 0.0001), Ferritin > 300 ng/ml (19/98 pts, p = 0.007), LDH > 300 (400) U/L, 51/87 pts, p = 0.004), presence of N-myc amplification (17/59 pts, p = 0.001), deletion of the short arm of chromosome 1 (19/74 pts, p < 0.0001) and di/tetraploidy (32/72 pts, p = 0.008). The power of these factors was even stronger in patients with localized disease whereas no significant prediction was observed for stage IV patients. Furthermore a significant correlation of the serological (NSE, ferritin, LDH) and biological factors (N-myc, deletion 1p, di/tetraploidy) was detected in this study. Only NSE was identified as an independent prognostic factor (p = 0.018) whereas no independent factor could be identified within the 3 biological parameters due to their high correlations (Kendall's tau for N-myc and deletion 1p:0.7). However, N-myc (p = 0.005) as well as deletion 1p (p = 0.01) were found significantly more important than di/tetraploidy. CONCLUSIONS: Biological classification of neuroblastomas should be mandatory and be the prerequisite for any risk adapted treatment. One serological and 2 biological factors could be a good standard evaluation to identify neuroblastoma patients at risk.\n\nHöfler, Gerald\n\nKerbl, Reinhold\n\nUrban, Ernst-Christian\n\n\n"
},
{
"text": "\n6007\nThe incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990.\n\nMostbeck, A\n\nGalvan, G\n\nBauer, P\n\nEber, O\n\nAtefie, K\n\nDam, K\n\nFeichtinger, H\n\nFritzsche, H\n\nHaydl, H\n\nKöhn, H\n\nKönig, B\n\nKoriska, K\n\nKroiss, A\n\nLind, P\n\nMarkt, B\n\nMaschek, W\n\nPesl, H\n\nRamschak-Schwarzer, S\n\nRiccabona, G\n\nStockhammer, M\n\nZechmann, W\n\nBeiträge in Fachzeitschriften\nISI:000073549700006\n9553166.0\n10.1007/s002590050234\nNone\nBetween 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over time, while GD did not.\n\n\n"
},
{
"text": "\n40102\nRandomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group.\n\nEbers, GC\n\nRice, G\n\nLesaux, J\n\nPaty, D\n\nOger, J\n\nLi DKB, Beall S, Devonshire V, Hashimoto S, Hooge J, Kastrukoff L, Krieger C, Mezei M, Seland P, Vorobeychi G, Morrison W, Nelson J, Freedman MS, Chrisie S, Nelson R, Rabinovitch H, Freedman C, Hartung HP, Rieckmann P, Archelos J, Jung S, Weilbach F, Flachenecke P, Sauer J, Hommes O, Jongen P, Brouwer S, McLeod J, Pollard J, Ng R, Sandberg-Wollheim M, Kallen K, Nilsson P, Ekberg R, Lundgren A, Jadback G, Wikstrom J, Multanen J, Valjakka M, Carton H, Lissoir F, Declerq I, Vieren M, Peeters E, Dubois B, Dekeersmaeker E, Van Herle A, Hughes RAC, Sharrack B, Soudain S, Panelius M, Eralinna J, Soilu-Hanninen M, Murto S, Medaer R, Broeckx J, Vanroose E, Bogaers A, Blumhardt LD, Edwards S, Liu C, Orpe V, Barnes D, Schwartz M, Stoy N, Harraghy C, Bertelsmann F, Uitdehaag B, Nasseri K, Chofflon M, Roth S, Kappos L, Huber S, Bellaiche Y, Senn C, King J, Jubert J, Whitten S, Newsom-Davis JM, Palace J, Lee M, Evangelou N, Pinto A, Cavey A, Sindic CJM, Monteyne P, Verougstraete D, Van Doorn PA, Moll W, Visser L, Willems M, Martina I, Buljevac D, Loman L, Bates D, Pandit D, Irving J, Rhodes B, Riddehough A, Zhao GJ, Wang X, Cheng Y, Ammoury N, Dupont F, Galazka A, Hyde R, Olson M, Pernin MO, Abdul-Ahad AK, Hommes O, Noseworthy J, Borden E, O'Brien P, Wolinsky J\n\nBeiträge in Fachzeitschriften\nISI:000076862300007\n9820297.0\n10.1016/S0140-6736(98)03334-0\nNone\nBACKGROUND: Previous trials of interferon beta in multiple sclerosis (MS) have shown efficacy, but the degree of clinical benefit remains uncertain, and the optimum dose is not known. We undertook a double-blind, placebo-controlled study in relapsing/remitting MS to investigate the effects of subcutaneous interferon beta-1a. METHODS: 560 patients with Kurtzke expanded disability status scale (EDSS) scores of 0-5.0, from 22 centres in nine countries, were randomly assigned subcutaneous recombinant interferon beta-1a 22 microg (n=189), or 44 microg (n=184), or placebo (n=187) three times a week for 2 years. Neurological examinations were done every 3 months. All patients had MRI twice yearly and 205 had monthly scans in the first 9 months of treatment. Analysis was by intention to treat. FINDINGS: Clinical data on 533 (95%) patients were available at 2 years. The relapse rate was significantly lower at 1 and 2 years with both doses of interferon beta-1a than with placebo (mean number per patient 1.82 for 22 microg group, 1.73 for 44 microg group vs 2.56 for placebo group: risk reductions 27% [95% CI 14-39] and 33 [21-44]). Time to first relapse was prolonged by 3 and 5 months in the 22 microg and 44 microg groups respectively, and the proportion of relapse-free patients was significantly increased (p<0.05). Interferon beta-1a delayed progression in disability, and decreased accumulated disability during the study. The accumulation of burden of disease and number of active lesions on MRI was lower in both treatment groups than in the placebo group. INTERPRETATION: Subcutaneous interferon beta-1a is an effective treatment for relapsing/remitting MS in terms of relapse rate, defined disability, and all MRI outcome measures in a dose-related manner, and it is well tolerated. Longer-term benefits may become clearer with further follow-up and investigation.\n\nArchelos-Garcia, Juan-Jose\n\n\n"
},
{
"text": "\n152319\nLong-term effects of weight-reducing diets in people with hypertension.\n\nSemlitsch, T\n\nJeitler, K\n\nBerghold, A\n\nHorvath, K\n\nPosch, N\n\nPoggenburg, S\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000373475200023\n26934541.0\n10.1002/14651858.CD008274.pub3\nNone\nAll major guidelines for antihypertensive therapy recommend weight loss. Thus dietary interventions that aim to reduce body weight might be a useful intervention to reduce blood pressure and adverse cardiovascular events associated with hypertension.\n Primary objectivesTo assess the long-term effects of weight-reducing diets in people with hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events). Secondary objectivesTo assess the long-term effects of weight-reducing diets in people with hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction.\n We obtained studies from computerised searches of the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Hypertension Specialised Register, Ovid MEDLINE, and Ovid EMBASE, and from searches in reference lists, systematic reviews, and the clinical trials registry ClinicalTrials.gov (status as of 2 February 2015).\n We included randomised controlled trials (RCTs) of at least 24 weeks' duration that compared weight-reducing dietary interventions to no dietary intervention in adults with primary hypertension.\n Two review authors independently assessed risk of bias and extracted data. We pooled studies using fixed-effect meta-analysis. In case of moderate or larger heterogeneity as measured by Higgins I(2), we used a random-effects model.\n This review update did not reveal any new studies, so the number of included studies remained the same: 8 studies involving a total of 2100 participants with high blood pressure and a mean age of 45 to 66 years. Mean treatment duration was 6 to 36 months. We judged the risk of bias as unclear or high for all but two trials. No study included mortality as a predefined outcome. One RCT evaluated the effects of dietary weight loss on a combined endpoint consisting of the necessity of reinstating antihypertensive therapy and severe cardiovascular complications. In this RCT, weight-reducing diet lowered the endpoint compared to no diet: hazard ratio 0.70 (95% confidence interval (CI), 0.57 to 0.87). None of the studies evaluated adverse events as designated in our protocol. There was low-quality evidence for a blood pressure reduction in participants assigned to weight loss diets as compared to controls: systolic blood pressure: mean difference (MD) -4.5 mm Hg (95% CI -7.2 to -1.8 mm Hg) (3 of 8 studies included in analysis), and diastolic blood pressure: MD -3.2 mm Hg (95% CI -4.8 to -1.5 mm Hg) (3 of 8 studies included in analysis). There was moderate-quality evidence for weight reduction in dietary weight loss groups as compared to controls: MD -4.0 kg (95% CI -4.8 to -3.2) (5 of 8 studies included in analysis). Two studies used withdrawal of antihypertensive medication as their primary outcome. Even though we did not consider this a relevant outcome for our review, the results of these studies strengthen the finding of reduction of blood pressure by dietary weight loss interventions.\n In this update, the conclusions remain the same, as we found no new trials. In people with primary hypertension, weight loss diets reduced body weight and blood pressure, however the magnitude of the effects are uncertain due to the small number of participants and studies included in the analyses. Whether weight loss reduces mortality and morbidity is unknown. No useful information on adverse effects was reported in the relevant trials.\n\nBerghold, Andrea\n\nHorvath, Karl\n\nJeitler, Klaus\n\nPoggenburg, Stephanie\n\nPosch, Nicole\n\nSemlitsch, Thomas\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n184130\nMeta-analysis uncovers genome-wide significant variants for rapid kidney function decline.\n\nGorski, M\n\nJung, B\n\nLi, Y\n\nMatias-Garcia, PR\n\nWuttke, M\n\nCoassin, S\n\nThio, CHL\n\nKleber, ME\n\nWinkler, TW\n\nWanner, V\n\nChai, JF\n\nChu, AY\n\nCocca, M\n\nFeitosa, MF\n\nGhasemi, S\n\nHoppmann, A\n\nHorn, K\n\nLi, M\n\nNutile, T\n\nScholz, M\n\nSieber, KB\n\nTeumer, A\n\nTin, A\n\nWang, J\n\nTayo, BO\n\nAhluwalia, TS\n\nAlmgren, P\n\nBakker, SJL\n\nBanas, B\n\nBansal, N\n\nBiggs, ML\n\nBoerwinkle, E\n\nBottinger, EP\n\nBrenner, H\n\nCarroll, RJ\n\nChalmers, J\n\nChee, ML\n\nChee, ML\n\nCheng, CY\n\nCoresh, J\n\nde Borst, MH\n\nDegenhardt, F\n\nEckardt, KU\n\nEndlich, K\n\nFranke, A\n\nFreitag-Wolf, S\n\nGampawar, P\n\nGansevoort, RT\n\nGhanbari, M\n\nGieger, C\n\nHamet, P\n\nHo, K\n\nHofer, E\n\nHolleczek, B\n\nXian Foo, VH\n\nHutri-Kähönen, N\n\nHwang, SJ\n\nIkram, MA\n\nJosyula, NS\n\nKähönen, M\n\nKhor, CC\n\nKoenig, W\n\nKramer, H\n\nKrämer, BK\n\nKühnel, B\n\nLange, LA\n\nLehtimäki, T\n\nLieb, W\n\nLifelines Cohort Study\n\nRegeneron Genetics Center\n\nLoos, RJF\n\nLukas, MA\n\nLyytikäinen, LP\n\nMeisinger, C\n\nMeitinger, T\n\nMelander, O\n\nMilaneschi, Y\n\nMishra, PP\n\nMononen, N\n\nMychaleckyj, JC\n\nNadkarni, GN\n\nNauck, M\n\nNikus, K\n\nNing, B\n\nNolte, IM\n\nO'Donoghue, ML\n\nOrho-Melander, M\n\nPendergrass, SA\n\nPenninx, BWJH\n\nPreuss, MH\n\nPsaty, BM\n\nRaffield, LM\n\nRaitakari, OT\n\nRettig, R\n\nRheinberger, M\n\nRice, KM\n\nRosenkranz, AR\n\nRossing, P\n\nRotter, JI\n\nSabanayagam, C\n\nSchmidt, H\n\nSchmidt, R\n\nSchöttker, B\n\nSchulz, CA\n\nSedaghat, S\n\nShaffer, CM\n\nStrauch, K\n\nSzymczak, S\n\nTaylor, KD\n\nTremblay, J\n\nChaker, L\n\nvan der Harst, P\n\nvan der Most, PJ\n\nVerweij, N\n\nVölker, U\n\nWaldenberger, M\n\nWallentin, L\n\nWaterworth, DM\n\nWhite, HD\n\nWilson, JG\n\nWong, TY\n\nWoodward, M\n\nYang, Q\n\nYasuda, M\n\nYerges-Armstrong, LM\n\nZhang, Y\n\nSnieder, H\n\nWanner, C\n\nBöger, CA\n\nKöttgen, A\n\nKronenberg, F\n\nPattaro, C\n\nHeid, IM\n\nBeiträge in Fachzeitschriften\nISI:000631134800001\n33137338.0\n10.1016/j.kint.2020.09.030\nPMC8010357\nRapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34, 74 cases, 107, 90 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19, 01 cases, 175, 44 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.\n Copyright © 2020 International Society of Nephrology. All rights reserved.\n\nGampawar, Piyush Gajananrao\n\nHofer, Edith\n\nRosenkranz, Alexander\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
}
]
}